Therapeutic polypeptides and proteins can be expressed in a variety of host cells including bacterial cells, E. coli cells, fungal or yeast cells, cells of a microorganism, insect cells, and mammalian cells. Fungal hosts such as the methylotrophic yeast Pichia pastoris has distinct advantages for therapeutic protein expression—e.g. it does not secrete high amounts of endogenous proteins, it has a strong inducible promoter, it can be grown in defined chemical media, and it can produce high titers of recombinant proteins (Cregg et al., Mol. Biotech. 16:23-52 (2000)). Yeast and filamentous fungi have both been successfully used for the production of recombinant proteins, both intracellular and secreted (Cereghino, J. L. and J. M. Cregg 2000 FEMS Microbiology Reviews 24(1): 45 66; Harkki, A., et al. 1989 Bio-Technology 7(6): 596; Berka, R. M., et al. 1992 Abstr. Papers Amer. Chem. Soc. 203: 121-BIOT; Svetina, M., et al. 2000 J. Biotechnol. 76(23): 245-251. S. cerevisiae is a remarkable host cell for expression of recombinant human serum albumin (HSA). However, the expression of other therapeutic polypeptides including polypeptides genetically fused with HSA faces the technical barriers of low titers of recombinant proteins.
Thus, there is a need for host cells, in particular S. cerevisiae strains, that are capable of producing heterologous peptides, polypeptides and/or proteins with high titers of a recombinant protein.